WO2016097242A1

WO2016097242A1 - Method for synthesizing optically active carbonyl compounds

Info

Publication number: WO2016097242A1
Application number: PCT/EP2015/080392
Authority: WO
Inventors: Mathias SCHELWIES; Rocco Paciello; Gunnar Heydrich; Günter WEGNER; Gerd Tebben; Martin Haubner; Andreas Keller; Oliver Bey; Stephanie RENZ; Georg Seeber
Original assignee: Basf Se
Priority date: 2014-12-19
Filing date: 2015-12-18
Publication date: 2016-06-23
Also published as: US10301244B2; EP3489213A1; US20180057437A1; EP3489213B1; ES2727384T3; CN107250091B; CN107250091A; US20180244598A1; US9975837B2; MX2017008170A; JP2017537965A; USRE49036E1; ES2883557T3; EP3233778A1; EP3233778B1; JP6702974B2

Abstract

The present invention relates to a method for synthesizing an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α,β-unsaturated carbonyl compound with hydrogen in the presence of at least one optically active transition metal catalyst which is soluble in the reaction mixture and comprises rhodium as catalytically active transition metal and a chiral, bidentate bisphosphine ligand; during the hydrogenation of the prochiral α,β-unsaturated carbonyl compound, the reaction mixture further comprises at least one compound of the general formula (I), in which R¹ and R² are identical or different and are C₆- to C₁₀-aryl which is unsubstituted or carries one or more, e.g. 1, 2, 3, 4 or 5, substituents selected from C₁- to C₆-alkyl, C₃- to C₆-cycloalkyl, C₆- to C₁₀-aryl, C₁- to C₆-alkoxy and amino; Z is a group CHR³R⁴ or aryl, which is unsubstituted or carries one or more, e.g. 1, 2, 3, 4 or 5, substituents selected from C₁- to C₆-alkyl, C₃- to C₆-cycloalkyl, C₆- to C₁₀-aryl, C₁- to C₆-alkoxy and amino, in which R³ and R⁴ are as defined in the claims and the description.

Description

Process for preparing optically active carbonyl compounds The present invention relates to a process for the preparation of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral

α, β-unsaturated carbonyl compound with hydrogen in the presence of at least one reaction mixture-soluble, optically active transition metal catalyst. Specifically, the present invention relates to a process for producing optically active aldehydes or ketones, in particular citronellal, by asymmetric hydrogenation of the corresponding prochiral α, β-unsaturated aldehydes or ketones.

BACKGROUND OF THE INVENTION Many optically active aldehydes and ketones are valuable intermediates in the synthesis of more highly refined chiral valuable and active ingredients or are themselves valuable fragrance and flavoring agents.

EP-A 0 000 315 relates to a process for the preparation of optically active citronellal by hydrogenation of geranial or neral in the presence of a dissolved in the reaction system catalyst complex of rhodium and a chiral phosphine.

T.-P. Dang et al. describe in J. Mol. Cat, 1982, Volume 16, pages 51-59, a method for the homogeneous catalytic hydrogenation of α, β-unsaturated aldehydes and the use of this method for the production of optically active citronellal. The catalysts used were complex compounds of a rhodium carbonyl compound and a chiral diphosphine.

Chapuis et al. mention in Helv. Chim. Acta, 2001, vol. 84, pages 230-242, footnote 4, the asymmetric hydrogenation of geranial or neral to optically active citronellal in the presence of a catalyst of Rh ₄ (CO) i2 and (R, R) -chiraphos (2R, 3R ) -2,3-bis (diphenylphosphino) butane.

A problem in the implementation of catalyzed (homogeneous) catalytic reactions catalyzed by soluble catalysts is the often insufficient stability of the catalyst complexes used or the resulting catalytically active Metallbzw. Transition metal complex compound. Against the background of the often high price of such catalysts or catalyst precursors, homogeneous catalytic reactions with complex transition metal catalysts can only be used on an industrial scale in an economical manner in special cases. JP-A 52078812 describes a process for the hydrogenation of α, β-unsaturated aldehydes such as crotonaldehyde, cinnamic aldehyde or α-methylcinnamaldehyde on homogeneous Rh catalysts under hydroformylation conditions in the presence of a triarylphosphine, a tertiary amine in stoichiometric amount and carbon monoxide.

WO 2006/040096 describes a process for preparing optically active carbonyl compounds by asymmetric hydrogenation of α, β-unsaturated carbonyl compounds with hydrogen in the presence of an optically active transition metal catalyst which is soluble in the reaction mixture and has at least one carbon monoxide ligand characterized in that the catalyst is pretreated with a gas mixture containing carbon monoxide and hydrogen and / or the asymmetric hydrogenation is carried out in the presence of additionally supplied carbon monoxide in the presence of the reaction mixture.

WO 2008/132057 likewise describes a process for the preparation of optically active carbonyl compounds by asymmetric hydrogenation of α, β-unsaturated carbonyl compounds, which is based on the process disclosed in WO 2006/040096. For better control of the carbon monoxide concentration in the reaction mixture during the hydrogenation, this method additionally includes the provisos that the pretreatment of the catalyst precursor with a gas mixture comprising 20 to 90 vol .-% carbon monoxide, 10 to 80% by volume of hydrogen and 0 to 5 vol. -% of other gases, wherein said volume percentages to 100 vol .-% complement, carried out at a pressure of 5 to 100 bar, separated from the catalyst thus obtained before use in the asymmetric hydrogenation excess carbon monoxide and the asymmetric hydrogenation in the presence of hydrogen with a carbon monoxide content of 100 to 1200 ppm.

Particularly in the case of the last-mentioned processes for the asymmetric hydrogenation of α, β-unsaturated carbonyl compounds, the stability or lifetime of the catalyst complexes used or the catalytically active metal or transition metal complex compound formed therefrom could be substantially improved compared to conventional processes. Due to moderate and fluctuating catalyst activities, these processes can be improved in terms of their conversion rates, especially if they are carried out on an industrial scale.

SUMMARY OF THE INVENTION

The object of the present invention was an improved process for the homogeneous catalytic asymmetric hydrogenation of α, β-unsaturated aldehydes or ketones To provide, which is characterized by improved catalyst activity with high enantiomeric selectivity to achieve high conversion rates with high product selectivity. Furthermore, the catalytic system should be characterized by a high stability and thus by an increased lifetime of the catalytically active, to be used in optically active form transition metal complex compound. The method should thereby be particularly suitable for applications on an industrial scale.

Surprisingly, it has been found that the catalytic activity of the optically active transition metal catalysts used for the homocatalytic asymmetric hydrogenation of prochiral α, β-unsaturated carbonyl compounds, the rhodium catalytically active transition metal, by the addition of a phosphine compound of the general formula (I), as defined below, can be significantly increased without significantly affecting their stability and selectivity in a significant way.

The present invention thus relates to a process for the preparation of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α, β-unsaturated carbonyl compound with hydrogen in the presence of at least one reaction mixture-soluble, optically active transition metal catalyst containing rhodium as a catalytically active transition metal and a chiral, bidentate bisphosphine ligand, wherein the reaction mixture additionally contains at least one compound of the general formula (I) during the hydrogenation of the prochiral α, β-unsaturated carbonyl compound:

wherein R ¹ , R ² : are the same or different and are C ₆ - to C ₀ -aryl which is unsubstituted or carries one or more, for example 1, 2, 3, 4 or 5, substituents which are selected under C ₁ - to C ₆ alkyl, C ₃ - to C ₆ cycloalkyl, C ₆ - to Cio-aryl, C ₁ - to C ₆ alkoxy and amino; Z is a group CHR ³ R ⁴ or aryl which is unsubstituted or carries one or more, for example 1, 2, 3, 4 or 5, substituents which are selected from C ₁ - to C ₆ -alkyl, C ₃ - to C ₆ cycloalkyl, C ₆ - to Ci ₀ aryl, d- to C ₆ alkoxy and amino, wherein R ³ alkyl of d- to C ₄ -alkyl, C to C ₄ -alkoxy-C to C _4, C ₃ - to C ₆ - cycloalkyl or C ₆ - to C ₀ is aryl, wherein one or two non-adjacent CH ₂ groups in C ₃ - to C ₆ -cycloalkyl may also be replaced by one or two oxygen atoms;

R ^{4 is} C 1 to C ₄ alkyl which is unsubstituted or a group

P (= O) R ^4a R ^4b bears, C _r to C ₄ alkoxy, C _r to C ₄ alkoxy C _r to C ₄ alkyl, C ₃ - to C ₆ cycloalkyl or C ₆ - to Cio Aryl, wherein one or two non-adjacent CH ₂ groups in C ₃ - to C ₆ -cycloalkyl may also be replaced by an oxygen atom and wherein C ₃ - to C ₆ -cycloalkyl and C ₆ - to Cio-aryl are unsubstituted or one or more, for example 1, 2, 3, 4 or 5, bear substituents which are selected from C 1 - to C ₄ -alkyl, C 1 - to C ₄ -alkoxy and amino; or

R ³ , R ⁴ : together with the C-atom to which they are attached, is C ₄ - to C ₈ -cycloalkyl, in which one or two non-adjacent CH ₂ -

Groups in C ₃ - to C ₆ cycloalkyl can also be replaced by one or two oxygen atoms and wherein C ₃ - to C ₆ cycloalkyl is unsubstituted or one or more, for example 1, 2, 3, 4 or 5, subsitutents which are selected from C 1 to C ₄ alkyl, C 1 to C ₄ alkoxy and AP (= O) R ^4a R ^4b , where A is a chemical bond or C 1 to C ₄ alkylene; and

R ^4a, R ^4b are identical or different and stand for phenyl which is un- substituted or one or more substituents, which are selected from d- to C ₆ alkyl, C ₃ - to C ₆ -cycloalkyl, C ₆ - to ciaryl, C ₁ to C ₆ alkoxy and amino.

Specifically, the present invention relates to a process for producing optically active aldehydes or ketones, in particular citronellal by asymmetric hydrogenation of the corresponding prochiral α, β-unsaturated aldehydes or ketones.

DETAILED DESCRIPTION OF THE INVENTION The process according to the invention is suitable for the preparation of optically active carbonyl compounds such as aldehydes, ketones, esters, lactones or lactams by asymmetric, ie enantioselective hydrogenation of the corresponding carbonyl compounds which have an ethylenic double bond in the α, β-position to the carbonyl group. According hydrogenated to the carbonyl α, β-ethylenic double bond in the presence of a soluble in the reaction mixture, optically active transition metal catalyst containing rhodium as a catalytically active transition metal, and a phosphine compound of general formula (I) to a carbon-carbon single bond, wherein the tetrahedral carbon atom thus newly created in the β-position carries four different substituents and is obtained in non-racemic form. Accordingly, in the context of the present invention, the term asymmetric hydrogenation is to be understood as meaning a hydrogenation in which the two enantiomeric forms of the hydrogenation product are not obtained in equal parts.

In the definitions of the variables given in the preceding and following formulas, collective terms are used which are generally representative of the respective substituents. The meaning C _n - to C _m - indicates the respective possible number of carbon atoms in the respective substituent or substituent part.

In the context of the present invention, the term "alkyl" encompasses unbranched or branched alkyl groups having 1 to 4, 6, 12 or 25 C atoms. These include, for example, C 1 - to C 6 -alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl,

1, 2-dimethylpropyl, 1, 1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 2-dimethylbutyl,

1, 3-dimethylbutyl, 2,3-dimethylbutyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl,

3,3-dimethylbutyl, 1, 1, 2-trimethylpropyl, 1, 2,2-trimethylpropyl, 1-ethylbutyl,

2-ethylbutyl, 1-ethyl-2-methylpropyl and the like. "Alkyl" is preferably unbranched or branched C 1 - to C 6 -alkyl groups.

In the context of the present invention, the term "cycloalkyl" includes cyclic, saturated hydrocarbon groups having 3 to 6, 12 or 25 carbon ring members, e.g. Cs-Cs-cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, or C7-Ci2-bicycloalkyl.

In the context of the present invention, the term "alkoxy" stands for an oxygen-bonded alkyl group having 1 to 6 C atoms, e.g. C 1 to C 6 alkoxy, such as methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy,

2-methylpropoxy, 1, 1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1, 1-dimethylpropoxy, 1, 2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy,

4-methylpentoxy, 1, 1-dimethylbutoxy, 1, 2-dimethylbutoxy, 1, 3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy,

2-ethylbutoxy, 1, 1, 2-trimethylpropoxy, 1, 2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy. It is preferable that "alkoxy" is Cr to C ₄ alkoxy.

In the context of the present invention, the term "alkenyl" encompasses unbranched or branched hydrocarbon radicals having 2 to 4, 6, 12 or 25 C atoms which contain at least one double bond, for example 1, 2, 3 or 4 double bonds. These include, for example, C 2 -C 6 alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butylene, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl , 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl,

3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl,

1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl,

2-methyl-3-butenyl, 3-methyl-3-butenyl, 1, 1-dimethyl-2-propenyl, 1, 2-dimethyl-1-propenyl, 1, 2-dimethyl-2-propenyl, 1-ethyl 1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl,

2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1 - Methyl 2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3 pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1, 1-dimethyl-2- butenyl,

1: 1 - dimethyl-3-butenyl, 1, 2-dimethyl-1-butenyl, 1, 2-dimethyl-2-butenyl, 1, 2-dimethyl-3-butenyl, 1, 3-dimethyl-1-butenyl, 1, 3-dimethyl-2-butenyl, 1, 3-dimethyl-3-butenyl,

2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl

3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2- Ethyl 1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl,

1, 1, 2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl. Alkenyl is preferably straight-chain C 2 - to C 12 -alkenyl groups or branched C 3 - to C 12 -alkenyl groups having in each case 1 to 3 double bonds, more preferably unbranched C 2 - to C 6 -alkenyl groups or branched C 3 - to C 6 -alkenyl groups one double bond each.

In the context of the present invention, the term "alkylene" refers to divalent hydrocarbon radicals having 2 to 25 carbon atoms. The divalent hydrocarbon radicals may be unbranched or branched. These include, for example, C 2 -C 16 -alkylene groups, such as 1, 4-butylene, 1, 5-pentylene, 2-methyl-1, 4-butylene, 1, 6-hexylene, 2-methyl-1, 5-pentylene, 3 Methyl-1, 5-pentylene, 1, 7-heptylene, 2-methyl-1,6-hexylene, 3-methyl-1,6-hexylene, 2-ethyl-1, 5-pentylene, 3-ethyl-1, 5-pentylene, 2,3- Dimethyl-1, 5-pentylene, 2,4-dimethyl-1, 5-pentylene, 1, 8-octylene, 2-methyl-1, 7-heptylene, 3-methyl-1, 7-hept len, 4-methyl -1, 7-heptylene, 2-ethyl-1, 6-hexylene, 3-ethyl-1, 6-hexylene, 2, 3-dimethyl-1, 6-hexylene, 2,4-dimethyl-1, 6-hexylene , 1, 9-nonylene, 2-methyl-1, 8-octylene, 3-methyl-1, 8-octylene, 4-methyl-1, 8-octylene, 2-ethyl-1, 7-heptylene, 3-ethyl -1, 7-heptylene, 1, 10-decylene, 2-methyl-1, 9-nonylene, 3-methyl-1, 9-nonylene, 4-methyl-1, 9-nonylene, 5-methyl-1, 9 -nonylene, 1,1,1-undecylene, 2-methyl-1, 10-decylene, 3-methyl-1, 10-decylene, 5-methyl-1, 10-decylene, 1, 12-dodecylene, 1, 13- Tridecylen, 1, 14-tetradecylene, 1, 15-pentadecylene, 1, 16-hexadecylene and the like. "Alkylene" is preferably unbranched C 2 - to C 12 -alkylene groups or branched C 3 - to C 12 -alkylene groups, in particular unbranched C 2 - to C 6 -alkylene groups or branched C 3 - to C 6 -alkylene groups.

In the case of the singly or multiply branched or substituted alkylene groups, the carbon atom at the branching point or the carbon atoms at the respective branching points or the substituent-carrying carbon atoms, independently of one another, can have an R, or an S configuration or both configurations in identical or different proportions exhibit.

In the context of the present invention, the term "alkenylene" refers to divalent hydrocarbon radicals having from 2 to 25 carbon atoms, which may be unbranched or branched, wherein the main chain has one or more double bonds, for example 1, 2 or 3 double bonds. These include, for example, C 2 - to cis-alkenylene groups, such as ethylene, propylene, 1-, 2-butylene, 1-, 2-pentylene, 1-, 2-, 3-hexylene, 1, 3-hexadienylene, 1, 4-hexadienylene , 1, 2, 3-heptylene, 1, 3-heptadienylene, 1, 4-heptydienylene, 2,4-heptadienylene, 1 -, 2, 3-octenylene, 1, 3

Octadienylene, 1,4-octadienylene, 2,4-octadienylene, 1-, 2-, 3-nonenyl, 1-, 2-, 3-, 4-, 5-decenylene, 1-, 2-, 3-, 4 -, 5-undecenylene, 2-, 3-, 4-, 5-, 6-dodecenylene, 2,4-dodecadienylene, 2,5-dodecadienylene, 2,6-dodecadienylene, 3-, 4-, 5-, 6 Tridecenylene, 2,5-tridecadienylene, 4,7-tridecadienylene, 5,8-tridecadienylene, 4, 5, 6, 7-tetradecenylene, 2,5-tetradecadienylene, 4,7-tetradecadienylene, 5,8-

Tetradecadienylene, 4-, 5-, 6-, 7-pentadecenylene, 2,5-pentadecadienylene, 4,7-pentadecadienylene, 5,8-pentadecadienylene, 1, 4,7-pentadecatrienylene, 4,7,1 1-pentadecatrienylene, 4,6,8-pentadecatrienylene, 4-, 5-, 6-, 7-, 8-hexadecenylene, 2,5-hexadecadienylene, 4,7-hexadecadienylene, 5,8-hexadecadienylene, 2,5,8-hexadecatrienylene, 4,8,1-hexadecatrienylene, 5,7,9-hexadecatrienylene, 5-, 6-, 7-, 8-heptadecenylene, 2,5-heptadecadienylene, 4,7-heptadecadienylene, 5,8-heptadecadienylene, 5- , 6-, 7-, 8-, 9-octadecenylene, 2,5-octadecadienylene, 4,7-octadecadienylene, 5,8-octadecadienylene and the like. Preferably it is at "alkenylene" unbranched C3- to Ci2-alkenylene or branched C ₄ - to Ci2-alkenylene groups each having one or two double bonds, in particular unbranched C3-Cs-alkenylene groups having a double bond. The double bonds in the alkenylene groups may independently exist in the E and Z configurations or as a mixture of both configurations. In the context of the present invention, the term "halogen" includes fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine or bromine.

In the context of the present invention, the term "aryl" encompasses one to three-membered aromatic ring system containing 6 to 14 carbon ring members. These include, for example, C6- to Cio-aryl, such as phenyl or naphthyl.

In the context of the present invention, the term "hetaryl" encompasses one to three-membered aromatic ring system containing 6 to 14 carbon ring members, one or more, for example 1, 2, 3, 4, 5 or 6, carbon atoms being replaced by a nitrogen, oxygen and / or sulfur atom. These include, for example, C3 to Cg-hetaryl groups, such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl,

3-Pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5- Oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1, 2,4-oxadiazol-3-yl, 1, 2,4-oxadiazol-5-yl, 1, 2, 4-thiadiazol-3-yl, 1, 2,4-thiadiazol-5-yl, 1, 2,4-triazol-3-yl, 1, 3,4-oxadiazol-2-yl, 1, 3,4- Thiadiazol-2-yl, 1, 3,4-triazol-2-yl, 2-pyridinyl, 3-pyridinyl,

4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1, 3,5-triazin-2-yl, 1, 2,4-triazine-3 yl, 2-indolyl, 3-indolyl, 4-indolyl,

5-indolyl, 6-indolyl, 7-indolyl and the like. Preferably, "hetaryl" is C5 to C6 hetaryl.

In the context of the present invention, the term "aralkyl" encompasses a mono- to binuclear aromatic ring system which is bonded via a straight-chain or branched C 1 -C 6 -alkyl group and contains 6 to 10 carbon ring members. These include, for example, C 7 to C 12 aralkyl such as phenylmethyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl and the like.

In the context of the present invention, the term "aralkyl" encompasses one to two-membered aromatic ring systems containing 6 to 10 carbon ring members which is substituted by one or more, for example 1, 2 or 3, unbranched or branched C 1 to C 6 -alkyl radicals. These include, for example, C7- to C12-alkylaryl, such as 1-methylphenyl, 2-methylphenyl, 3-methylphenyl, 1-ethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 1-propylphenyl, 2-propylphenyl, 3-propylphenyl, 1-iso Propylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 1-butylphenyl, 2-butylphenyl, 3-butylphenyl, 1-iso-butylphenyl, 2-iso-butylphenyl, 3-iso-butylphenyl, 1-sec-butylphenyl , 2-sec-butylphenyl, 3-sec-butylphenyl, 1-tert-butylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, Butylphenyl, 1- (1-pentenyl) phenyl, 2- (1-pentenyl) phenyl, 3- (1-pentenyl) phenyl, 1- (2-pentenyl) phenyl, 2- (2-pentenyl) phenyl, 3- ( 2-pentenyl) phenyl, 1- (3-pentenyl) phenyl, 2- (3-pentenyl) phenyl, 3- (3-pentenyl) phenyl, 1- (1- (2-methylbutyl)) phenyl, 2- (1 - (2-methylbutyl)) phenyl, 3- (1- (2-methylbutyl)) phenyl, 1- (2- (2-methylbutyl)) phenyl, 2- (2- (2-methylbutyl)) phenyl, 3- (2- (2-methylbutyl)) phenyl, 1- (3- (2-methylbutyl)) phenyl, 2- (3- (2-methylbutyl)) phenyl, 3- (3- (2-methylbutyl)) phenyl, 1 - (4- (2-methylbutyl)) phenyl, 2- (4- (2-methylbutyl)) phenyl, 3- (4- (2-methylbutyl)) phenyl, 1- (1 - (2,2-dimethylpropyl )) phenyl, 2- (1- (2,2-dimethylpropyl)) phenyl, 3- (1- (2,2-dimethylpropyl)) phenyl, 1- (1-hexenyl) phenyl, 2- (1-hexenyl) phenyl, 3- (1-hexenyl) phenyl, 1- (2-hexenyl) phenyl, 2- (2-hexenyl) phenyl, 3- (2-hexenyl) phenyl, 1- (3-hexenyl) phenyl, 2- 3-hexenyl) phenyl, 3- (3-hexenyl) phenyl, 1- (1- (2-methylpentenyl)) phenyl, 2- (1- (2-methylpentenyl)) phenyl, 3- (1- (2-methylpentenyl )) phenyl, 1- (2- (2-methylpe phenyl), 2- (2- (2-methylpentenyl)) phenyl, 3- (2- (2-methylpentenyl)) phenyl, 1- (3- (2-methylpentenyl)) phenyl, 2- (3- (3-naphthyl) phenyl) 2-methylpentenyl)) phenyl, 3- (3- (2-methylpentenyl)) phenyl, 1- (4- (2-methylpentenyl)) phenyl, 2- (4- (2-methylpentenyl)) phenyl, 3- (4 - (2-methylpentenyl)) phenyl, 1- (5- (2-methylpentenyl)) phenyl, 2- (5- (2-methylpentenyl)) phenyl, 3- (5- (2-methylpentenyl)) phenyl, 1 - (1- (2,2-dimethylbutenyl)) phenyl, 2- (1- (2,2-dimethylbutenyl)) phenyl, 3- (1- (2,2-dimethylbutenyl)) phenyl, 1- (3- (2 , 2-dimethylbutenyl)) phenyl, 2- (3- (2,2-dimethylbutenyl)) phenyl, 3- (3- (2,2-dimethylbutenyl)) phenyl, 1- (4- (2,2-dimethylbutenyl) ) phenyl, 2- (4- (2,2-dimethylbutenyl)) phenyl, 3- (4- (2,2-dimethylbutenyl)) phenyl and the like.

In a preferred embodiment of the method according to the invention compounds of the formula (I) are used, wherein Z in formula (I) is a group CHR ³ R ⁴ . Among these, preference is given to those compounds of the general formula (I) in which the variables R ¹ , R ² , R ³ , R ⁴ independently of one another and in particular jointly have the following meanings: R ¹ , R ² : are identical or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents selected from methyl and methoxy, wherein R ¹ and R ^{2 are} each in particular unsubstituted phenyl; R ³ is C ¹ to C 4 alkyl, in particular methyl; R ⁴ is C 1 - to C ⁴ -alkyl which is unsubstituted or carries a group P (= O) R ^4a R ^4b , where R ^{4 is} in particular methyl or ethyl or a group CH ₂ -P (= O) R ^4a R ^4b or CH (CH ₃ ) -P (= O) R ^4a R ^4b ; or R ³ , R ⁴ : together with the C atom to which they are bonded, for C ³ to Cs

Cycloalkyl in which one or two Ch groups can be replaced by one or two nonadjacent oxygen atoms and where C3- to C6-cycloalkyl is unsubstituted or bears a group AP (= O) R ^4a R ^4b and / or 1,

2, 3 or 4 methyl groups as substituents, wherein R ³ and R ⁴ together with the carbon atom to which they are bonded, in particular for cyclopentyl, oxolan-3-yl, 2,2-dimethyl-1, 3-dioxolane-4 -yl or cyclohexyl, or R ³ and R ⁴ , together with the carbon atom to which they are attached, may be bicyclo [2.2.1] heptan-1-yl;

Postion has a group P (= 0) R ^4a R ^4b ; where A is a chemical bond, CH 2 or CH (CH 3); and

R ^4a , R ^4b : are the same or different and are C6- to Cio-aryl and in particular phenyl, which is unsubstituted or carries 1, 2 or 3 substituents selected from methyl and methoxy, wherein R ^4a and R ^4b in particular are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy, with particular preference R ^4a and R ^{4b are} each unsubstituted phenyl.

In a particularly preferred embodiment of the process according to the invention compounds of the formula (I) are used, wherein Z in formula (I) is a group CHR ³ R ⁴ and wherein the variables R ¹ , R ² , R ³ , R ^{4 are} independently and in particular together have the following meanings:

R ¹ , R ² : are the same or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy, wherein R ¹ and R ^{2 are} each particularly unsubstituted phenyl;

R ³ is Cr to C ₄ alkyl, especially methyl; R ⁴ is C 1 - to C ₄ -alkyl which carries a group P (= O) R ^4a R ^4b , where and in particular a group CH ₂ -P (= O) R ^4a R ^4b or CH (CH ₃ ) - P (= 0) R ^4a R ^4b . in which R ^4a , R ^4b : are identical or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy, R ^4a and R ^4b particularly preferably in each case being unsubstituted phenyl ,

In this particularly preferred embodiment of the process according to the invention, use is made in particular of a compound of the formula (I) in which

R ¹ , R ² : represent unsubstituted phenyl;

R ^{3 is} methyl;

R ^{4 is} a group CH (CH ₃ ) -P (= O) R ^4a R ^4b wherein R ^4a and R ^{4b are} each unsubstituted phenyl.

This is the compound (2- (diphenylphosphoryl) -1-methylpropyl)) -diphenylphosphine, including its (R, R) enantiomers (= (R, R) - chiraphosmonooxide) and its (S, S) -enantiomers (= (5, S) -Chiraphosmonooxid) and its racemate (compounds (1-1)).

If the radicals R ³ and R ⁴ in the general formula (I) have different meanings or together with the carbon atom to which they are attached represent a bicyclic and / or substituted cycloalkyl radical, the carbon atom which contains the radicals R ³ and R ^{4 has} an (R) or (S) configuration. These compounds of the general formula (I) can be used as pure (R) - or pure (S) -

Stereoisomers or as mixtures thereof. As a rule, the pure (R) and (S) stereoisomers will be used in these cases, although any stereoisomer mixtures are also suitable for use in the present process. A pure stereoisomer is understood here and below to mean chiral substances which, with respect to the desired stereoisomer, have an enantiomeric excess (ee) of at least 80% ee, in particular at least 90% ee and especially at least 95% ee. In another embodiment of the process according to the invention compounds of the formula (I) are used, wherein Z in formula (I) is aryl which is unsubstituted or carries one or more, for example 1, 2, 3, 4 or 5 substituents selected are C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, C 6 to C 10 aryl, C 1 to C 6 alkoxy and amino ,. Among these, preference is given to those compounds of the general formula (I) in which the variables R ¹ , R ² , Z independently of one another and in particular jointly have the following meanings: Z is phenyl which is unsubstituted or carries 1, 2 or 3 substituents selected from methyl and methoxy; R ¹ , R ² : are the same or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy, wherein R ¹ and R ^{2 are} each particularly unsubstituted phenyl. Particularly preferred compounds of the general formula (I) are, for example:

(2- (Diphenylphosphoryl) -1-methylpropyl)) -diphenylphosphine, including its (R, R) -enantiomers (=

and its (S, S) -enantiomers (= (5, S) -chiraphosmonoxide) and its racemates (compounds (1-1)),

Cyclopentyldiphenylphosphine (compound (I-2)

2-butyldiphenylphosphine (compound (I-3)

Cyclohexyldiphenylphosphine (Compound (I-4),

Isopropyldiphenylphosphine (compound (I-5),

[5- (diphenylphosphanylmethyl) -2,2-dimethyl-1,3-dioxolan-4-yl] methyl-diphenyl-phosphine monoxide, including its (4S, 5S) and ^, 5'-enantiomers and its racemate ( Compounds (I-6),

[5- (1-diphenylphosphanylethyl) -2,2-dimethyl-1,3-dioxolan-4-yl] ethyl-diphenylphosphine monoxide, including its (4S, 5S) and ^, 5'-enantiomers and its Racemates (compounds (I-7),

- [2-diphenylphosphinylcyclohexyl] -diphenyl-phosphine monoxide, including its (1S, 2S) -

/?,.? ?, l-enantiorriers and its racemates (compounds (I-8),

[4-diphenylphosphanyltetrahydrofuran-3-yl] -diphenylphosphine monoxide, including its (3S, 4S) -

and its racemate (Compounds (I-9),

[2-Diphenylphosphanyl-3-bicyclo [2.2.1] hept-5-enyl] -diphenyl-phosphine monoxide, including its (1S, 2R, 3R, 4R) -, (1R, 2S, 3R, 4R) -, ( 1S, 2R, 3S, 4S) -,

(1R, 2S, 3S, 4SJAsomers, and their enantiomer and diastereomer mixtures (compounds (1-10),

- [1-benzyl-4-diphenylphosphinyl-pyrrolidin-3-yl] -diphenyl-phosphine monoxide, including its (3S, 4S) -

and its racemate (compounds (1-1 1), [3-diphenylphosphino-1-methylbutyl] -diphenyl-phosphine monoxide, including its (1S, 3S) -

and its racemate (compounds (1-12),

and their mixtures.

Also suitable is triphenylphosphine (compound (1-13)) and mixtures thereof with one or more of the aforementioned compounds of formula (I), e.g. with one of the compounds (1-1) to (1-12). In the process according to the invention, the compound of the formula (I) is generally used in an amount of 0.01 to 1 mol, preferably 0.02 to 0.8 mol, more preferably 0.03 to 0.7 mol, and in particular in one Amount of 0.05 to 0.6 mol per mole of rhodium. Suitable starting materials in the process according to the invention are generally all types of prochiral carbonyl compounds which have a double bond at the 2-position. The prochiral α, β-unsaturated carbonyl compound is preferably prochiral, α, β-unsaturated ketone or, in particular, prochiral, α, β-unsaturated aldehydes.

Accordingly, the process according to the invention is preferably suitable for the preparation of optically active aldehydes or ketones by asymmetric hydrogenation of prochiral α, β-unsaturated aldehydes or ketones. The process according to the invention is particularly preferably suitable for the preparation of optically active aldehydes by asymmetric hydrogenation of prochiral α, β-unsaturated aldehydes.

In a preferred embodiment of the process according to the invention, the prochiral α, β-unsaturated carbonyl compound is selected from compounds of the general formula (II)

R ⁵ , R ⁶ are different from each other and each represents an unbranched, branched or cyclic Kohlenwassestoffrest having 1 to 25 carbon atoms, which is saturated or one or more, for example, 1, 2, 3, 4 or 5, preferably non-conjugated ethylenic double bonds , and which is unsubstituted or one or more, for example 1, 2, 3 or 4, identical or different carries different substituents selected from OR ⁸ , NR ^9a R ^9b , halogen, C6 to Cio-aryl and C3 to Cg-hetaryl; is hydrogen or an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more, for example 1, 2, 3, 4 or 5, preferably non-conjugated, ethylenic double bonds and which is unsubstituted or one or more, for example 1, 2, 3 or 4, bears the same or different substituents which are selected from OR ⁸ , NR ^9a R ^9b , halogen, Ce to Cio-aryl and C3 to Cg-hetaryl;

together with one of the radicals R ⁵ or R ^{6 may} also denote a 3 to 25-membered alkylene group in which 1, 2, 3 or 4 non-adjacent CH 2 groups may be replaced by O or NR ^9c , the alkylene group being saturated or one or more, for example, 1, 2, 3, 4 or 5, preferably non-conjugated ethylenic double bonds, and wherein the alkylene group is unsubstituted or carries one or more, for example 1, 2, 3 or 4, identical or different substituents which are selected from OR ⁸ , NR ^9a R ^9b , halogen, C ₁ - to C ₄ alkyl, C ₆ - to Cio-aryl and C ₃ - to Cg-hetaryl, where two substituents also together represent a 2- to 10-membered alkylene group wherein the 2- to 10-membered alkylene group is saturated or has one or more, eg 1, 2, 3 or 4, non-conjugated ethylenic double bonds, and wherein the 2- to 10-membered alkylene group is unsubstituted or one or more , eg 1, 2, 3 or 4, same or ver carries different substituents selected from OR ⁸ , NR ^9a R ^9b , halogen, C6 to Cio-aryl and C3 to Cg-hetaryl;

is hydrogen, C ₁ - to C ₆ -alkyl, C ₆ - to Cio-aryl, C ₇ - to C ₂ -aralkyl or C 1 -C 12 -alkylaryl; R ^9a , R ^{9b are} each independently hydrogen, C 1 to C 6 alkyl, C 6 to C 10 aryl, C 7 to C 12 aralkyl or C 7 to C 12 alkylaryl or

R ^9a and R ^9b together also an alkylene chain having 2 to 5 carbon atoms, the

may be interrupted by N or O may mean; and R ^9c is hydrogen, d- to C ₆ alkyl, C ₆ - to C ₂ is aralkyl or alkylaryl Orbis Ci2 - to Cio-aryl, C. ₇

The unbranched, branched or cyclic hydrocarbyl radicals having 1 to 25 carbon atoms mentioned in the definitions of radicals R ⁵ , R ⁶ and R ⁷ are generally unbranched C 1 to C 25 alkyl groups, unbranched C 2 to C 25 Alkenyl groups, unbranched C ₄ to C 25 alkadienyl groups, branched C ₃ to C 25 alkyl groups, branched C ₃ to C 25 alkenyl groups, branched C 5 to C 25 alkadienyl groups, and C ₃ to C 25 cycloalkyl groups or C ₃ to C ₄ - Cycloalkyl groups which are substituted by one or more, for example by 1, 2, 3 or 4 Cr to C ₄ - alkyl groups, as defined above. The cyclic hydrocarbon radicals also include those cyclic hydrocarbon radicals which have a phenyl ring which optionally carries one or more, for example 1, 2, 3, 4, 5 or 6 Ci-C ₄ - alkyl groups, wherein the phenyl ring directly to the ethylenically unsaturated double bond or the carbonyl group is bonded in formula (II) or is bonded via a C 1 -C 6 -alkylene group.

By an alkenyl group is meant a linear or branched aliphatic hydrocarbon radical which is monounsaturated. By an alkadienyl group is meant a linear or branched aliphatic hydrocarbon radical which is diunsaturated. The 3- to 25-membered alkylene groups mentioned in the definition of the radical R ⁷ , which are saturated, are generally straight-chain or branched C 3 - to C 25 -alkylene groups, as defined above. The 3- to 25-membered alkylene groups mentioned in the definition of the radical R ⁷ which have one or more, for example 1, 2, 3 or 4, non-conjugated ethylenic double bonds are generally branched or unbranched C 3 -alkyl radicals. to C25 alkenylene groups, as previously defined. Preferably, one of R ⁵ , R ^{6 is} methyl or ethyl, in particular methyl, and the other is an unbranched, branched or cyclic hydrocarbon radical having from 3 to 25 carbon atoms which is saturated or one or more, eg 1, 2 , 3, 4 or 5, preferably non-conjugated ethylenic double bonds, and which is unsubstituted or carries one or more, eg 1, 2, 3 or 4, identical or different substituents selected from OR ⁸ , NR ^9a R ^9b , Halogen, C ₆ - to Cio-aryl and C ₃ - to Ce-hetaryl.

In particular, one of the radicals R ⁵ , R ^{6 is} methyl or ethyl, in particular methyl, and the other radical is an unbranched, branched or cyclic hydrocarbon radical having 3 to 25 carbon atoms, which is saturated or has one or more radicals. Rere, for example, 1, 2 or 3, preferably having non-conjugated ethylenic double bonds.

R ⁷ is in particular hydrogen.

In a very preferred embodiment of the process according to the invention, the prochiral α, β-unsaturated carbonyl compound is selected from compounds of the general formula (IIa) and (IIb)

wherein

R ⁵ , R ^{6 is in} each case an unbranched or branched hydrocarbon residue with 2 to 25, in particular with 3 to 20 carbon atoms, which is saturated or has 1, 2, 3, 4 or 5 non-conjugated ethylenic double bonds

Accordingly, with the inventive method by asymmetric hydrogenation of prochiral α, β-unsaturated aldehydes or ketones of the general formulas (II), (IIa) and (IIb), the corresponding α, β-saturated aldehydes or ketones of the formula (III) in optically produce active form, wherein the carbon atom which carries the radicals R ⁵ and R ⁶ represents the center of asymmetry generated by the hydrogenation.

In formula (III), R ⁵ , R ⁶ and R ^{7 have} the meanings given for formula (II), in particular those given for formulas (IIa) and (IIb).

The asymmetric, ie enantioselective, hydrogenation of the α, β-unsaturated aldehydes of the formulas (IIa) or (IIb) according to the invention gives access to the corresponding α, β-saturated aldehydes. The compounds of the formulas (IIa) and (IIb) represent E / Z double bond isomers to each other. In principle, the corresponding optically active aldehydes starting from both double bond isomers of the formulas (IIa) and (IIb) are accessible. Depending on the choice of the enantiomeric form of the catalyst, ie depending on the choice of the (+) - or (-) - enantiomer of the catalyst or the (+) - or (-) - Enantiomers of the chiral ligand used, obtained in accordance with the invention from the E or Z double bond isomers used preferably one of the enantiomers of the optically active aldehyde. The same applies to the abovementioned substrate or product classes. In principle, mixtures of the two double bond isomers can also be reacted in accordance with the invention. This gives mixtures of the two enantiomers of the desired target compound.

Examples of optically active aldehydes or ketones which can be prepared by the process according to the invention include the following compounds:

(IH-2) (IH-3) (NW) (IH-5)

The process according to the invention is particularly preferably suitable for the preparation of optically active citronellal of the formula (IV)

in which ^{* designates} the center of asymmetry; by asymmetric hydrogenation of a compound of the formula (IIa-1) or of a compound of the formula (IIb-1)

It is also possible to react mixtures of geranial and neral in accordance with the invention to obtain, as described above, mixtures of D- or L-citronellal which are optically active if the two enantiomers are not present in equal parts therein. In the context of the process according to the invention, the preparation according to the invention of D-citronellal by asymmetric hydrogenation of neral or geranial is particularly preferred.

The preparation process according to the invention is carried out in the presence of a reaction mixture-soluble, optically active transition metal catalyst containing rhodium as a catalytically active transition metal.

Such catalysts are obtainable, for example, by reacting at least one suitable rhodium compound which is soluble in the reaction mixture with an optically active ligand which has at least one phosphorus and / or arsenic atom.

Suitable rhodium compounds are, in particular, those which are soluble in the chosen reaction medium, such as, for example, rhodium (0), rhodium (I), rhodium (II) and rhodium (III) salts, such as e.g. Rhodium (III) chloride, rhodium (III) bromide, rhodium (III) nitrate, rhodium (III) sulfate, rhodium (II) or rhodium (III) oxide, rhodium (II) or rhodium (III) acetate, rhodium (II) or rhodium (III) carboxylate, Rh (acac) 3,

[Rh (cod) Cl] ₂ , [Rh (cod) ₂ ] BF ₄ , Rh ₂ (OAc) ₄ , bis (ethylene) rhodium (I) acac, Rh (CO) ₂ acac, [Rh (cod) OH] ₂ , [Rh (cod) OMe] ₂ , Rh ₄ (CO) i ₂ or Rh ₆ (CO) i ₆ , where "acac" is an acetylacetonate ligand, "cod" is a cyclooctadiene ligand and "OAc stands for an acetate ligand. Rh (OAc) 3, [Rh (cod) Cl] 2, Rh (CO) 2 acetylacetonate, [Rh (cod) OH] ₂ , [Rh (cod) OMe] ₂ , Rh ₄ (CO ) i ₂ or Rh ₆ (CO) i ₆ , Rh ₂ (OAc) ₄ and bis (ethylene) rhodium (l) acetylacetonate used. In particular, Rh (CO) ₂ acac, Rh ₂ (OAc) ₄ and bis (ethylene) rhodium (l) acetylacetonate are used as the rhodium compound.

The abovementioned and other suitable rhodium compounds or rhodium complexes are known and adequately described in the literature or can be prepared by a person skilled in the art analogously to the compounds already known.

The stated rhodium compounds or rhodium complexes are used according to the invention usually in an amount of about 0.001 to about 1 mol%, preferably from about 0.002 to about 0.5 mol%, in particular from about 0.005 to about 0.2 mol% (relative on the transition metal atoms contained) in relation to the amount of substrate to be hydrogenated.

In reactions carried out under continuous conditions, the ratio of the amount of transition metal compound used as precursor of the homogeneous catalyst according to the invention to the amount of substrate to be hydrogenated is advantageously chosen such that a catalyst concentration in the range from about 100 ppm to 10000 ppm, in particular in the range of about 200 ppm up to 5000 ppm is maintained.

According to the invention, said rhodium compounds or rhodium complexes are brought into contact with another compound which is optically active, preferably substantially enantiomerically pure (ie an enantiomeric excess of at least 90% ee, in particular at least 95% ee or at least 98% ee or at least 99% % ee) and has two phosphorus atoms. This compound, referred to as the chiral ligand, forms the transition metal catalyst to be used according to the invention in the reaction mixture or in a preforming stage upstream of the hydrogenation with the transition metal compound used.

According to the invention, such chiral ligands are used which have two phosphorus atoms and form chelate complexes with the transition metal used, and which are referred to below as bidentate bisphosphine ligands.

Suitable chiral bidentate bisphosphine ligands in the context of the present invention are those compounds as described, for example, in: I. Ojima (ed.), Catalytic Asymmetry Synthesis, Wiley-VCh, 2nd edition, 2000 or in EN Jacobsen, A Pfaltz, H. Yamamoto (ed.), Comprehensive Asymmetry Catalysis, 2000, Springer or in W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029-3069. By way of example, the following compounds may be mentioned as chiral ligands (1) to (90) which can preferably be used according to the invention and their enantiomers:

(4) (5) (6)

(36) (37) (38) (39)

(76) (77) (78) (79)

In the formulas (1) to (90), "Ph" is phenyl, "Cy" is cyclohexyl, "xyl" is xylyl, "Toi" is p-tolyl and "Bn" is benzyl.

Particularly preferred ligands according to the invention are those of the structural formulas (1) to (14) and (37), (38), (41), (43), (49), (50), (51), (52), (65 ), (66), (67), (68), (69), (71), (72), (73), (74), (75), (83), (84), (85), (86), (87). Particularly preferred chiral, bidentate bisphosphine ligands are those of the general formulas (IX), (X) or (XI)

wherein

R ¹¹ . Each R ¹² is independently an unbranched, branched or cyclic hydrocarbon radical of 1 to 20 carbon atoms which is saturated or may have one or more, usually 1 to about 4, non-conjugated ethylenic double bonds and which is unsubstituted or or several, usually 1 to 4, identical or different substituents which are selected from OR ¹⁹ , NR ²⁰ R ²¹ , halogen, C ₆ -Cio-aryl and Cs-Cg-hetaryl, or

R ¹¹ and R ¹² together may also denote a 2 to 10 membered alkylene group or a 3 to 10 membered cycloalkylene group wherein 1, 2, 3 or 4 nonadjacent Ch groups may be replaced by O or NR ^9c , the alkylene group and the cycloalkylene group is saturated or has one or two non-conjugated ethylenic double bonds, and wherein the alkylene group and the cycloalkylene group are unsubstituted or carry one or more identical or different substituents selected from C 1 to C ₄ alkyl;

R ¹³ , R ^{14 are} each independently of one another hydrogen or straight-chain or branched C 1 - to C ₄ -alkyl and

R ¹⁵ , R ¹⁶ , R ¹⁷ , R ^{18 are the} same or different and are C ⁶ to C 10 aryl which is unsubstituted or carries one or more substituents selected from C 1 to C 6 alkyl, C 3 to C6 cycloalkyl, C6 to Cio aryl, C6 to C6 alkoxy and amino; R ¹⁹ , R ²⁰ , R ²¹ : each independently of one another denote hydrogen, C 1 -C 4 -alkyl, C 6 -C 10 -aryl, C 7 -C 12 -aralkyl or C 7 -C 12 -alkylaryl, where R ²⁰ , R ²¹ : together also form an alkylene chain having 2 to 5 carbon atoms which may be interrupted by N or O may mean.

With regard to the formulas (IX), (X) and (XI), the variables have in particular the following meaning:

R ¹¹ , R ¹² : each independently represent an unbranched, branched or C ₄ to C ₄ alkyl radical or

R ¹¹ and R ¹² together or for a C 3 to Cz alkanediyl radical, C 3 bis

C7 alkenediyl radical, C5 to C7 cycloalkanediyl radical or a C5 bis

C7-cycloalkenediyl radical, where the four radicals mentioned above are unsub- stituiert or one or more identical or different substituents which are chosen from C to C ₄ alkyl; R ¹³ , R ¹⁴ : each independently of one another denote hydrogen or straight-chain or branched C ₄ -C ₄ -alkyl and

R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ : represent phenyl.

Particularly preferred chiral, bidentate bisphosphine ligands in the context of the process according to the invention are those of the general formula (IX), in particular the compounds of the formula (1) or of the formulas (IXa) or (IXb) referred to below as "chiraphos",

Ph ₂ P PPh ₂ Ph ₂ P PPh ₂

(IXa) (IXb)

Also suitable are the compounds of the formula (5) or of the formulas (IXc) or (IXd) denoted "norphos",

(IXc) (IXd)

In the formulas (IXa) to (IXd), Ph is phenyl.

The selected chiral ligands are used according to the invention in each case in the form of one of its two enantiomers. The chiral ligands typically have an enantiomeric excess (ee) of at least 80% ee, especially at least 90% ee and especially at least 95% ee.

When using chiral ligands having two phosphorus atoms, these are used advantageously in an amount of about 0.9 to about 10 mol, preferably about 1 to about 4 mol per mol of transition metal compound employed. The optically active rhodium catalyst which is soluble in the reaction mixture is preferably generated in situ by reacting an achiral rhodium compound and with a chiral, bidentate bisphosphine ligand before or during the hydrogenation.

In this context, the term "in situ" means that the catalyst is generated directly before or at the beginning of the hydrogenation. The catalyst is preferably generated before the hydrogenation.

In a preferred embodiment of the process according to the invention, the catalyst is pretreated before the hydrogenation with a gas mixture containing carbon monoxide and hydrogen and / or the asymmetric hydrogenation is carried out in the presence of additionally supplied carbon monoxide in the presence of the reaction mixture.

This means that the reaction mixture, ie homogeneous rhodium catalyst used, is pretreated either before the asymmetric hydrogenation with a gas mixture containing carbon monoxide and hydrogen (ie carrying out a so-called preformation) or the asymmetric hydrogenation in the presence of the reaction mixture additionally supplied carbon monoxide performs or performs a preforming and then the asymmetric hydrogenation in Presence of the reaction mixture additionally supplied carbon monoxide performs.

In this preferred embodiment, the catalyst is preferably pretreated with a gas mixture containing carbon monoxide and hydrogen, and the asymmetric hydrogenation is carried out in the presence of additionally fed carbon monoxide in the presence of the reaction mixture.

The rhodium catalysts which are soluble in the reaction mixture and which are used in this preferred embodiment can therefore have at least one CO ligand at least in a catalytic cycle or in a preform upstream of the actual catalytic cycle, it being immaterial whether these have at least one CO molecule. Having ligand-containing catalyst form represents the actual catalytically active catalyst form. In order to stabilize the catalyst forms which may have CO ligands, it may be advantageous to additionally supply carbon monoxide to the reaction mixture during the hydrogenation.

In this preferred embodiment, said pretreatment of the catalyst precursor is carried out with a gas mixture comprising 20 to 90% by volume of carbon monoxide, 10 to 80% by volume of hydrogen and 0 to 5% by volume of further gases, said volume proportions being 100% Vol .-% complete, carried out at a pressure of 5 to 100 bar. In addition, excess carbon monoxide is separated from the catalyst thus obtained before use in the asymmetric hydrogenation. The term excess carbon monoxide is to be understood as meaning carbon monoxide which is contained in the resulting reaction mixture in gaseous or dissolved form and is not bound to the transition metal catalyst or its precursor. Accordingly, the excess, non-catalyst bound carbon monoxide is at least substantially removed, i. to the extent that any residual amounts of dissolved carbon monoxide in the following hydrogenation is not disturbing. This is usually ensured when about 90%, preferably about 95% or more of the carbon monoxide used for preformation are separated. Preferably, the excess carbon monoxide is completely removed from the catalyst obtained by preforming.

The separation of the excess carbon monoxide from the catalyst obtained or from the catalyst-containing reaction mixture can be carried out in various ways. Preferably, the catalyst or the catalyst obtained by preforming is depressurized. holding, the catalyst-containing mixture to a pressure of up to about 5 bar (absolute), preferably, especially when performing the preforming in the pressure range of 5 to 10 bar, to a pressure of less than 5 bar (absolute), preferably one Pressure in the range of about 1 bar to about 5 bar, preferably 1 to less than 5 bar, more preferably to a pressure in the range of 1 to 3 bar, most preferably to a pressure in the range of about 1 to about 2 bar, in particular preferably to normal pressure, so that gaseous, unbound carbon monoxide escapes from the product of preforming. The abovementioned expansion of the preformed catalyst can be carried out, for example, by using a high-pressure separator, as is known per se to the person skilled in the art. Such separators in which the liquid is in the continuous phase are described, for example, in: Perry's Chemical Engineers' Handbook, 1997, 7th Ed., McGraw-Hill, pp. 14.95 and 14.96; the prevention of a possible drop rash is described on pages 14.87 to 14.90. The relaxation of the preformed catalyst can be carried out in one or two stages until reaching the desired pressure in the range from 1 bar to about 5 bar, wherein the temperature usually drops to 10 to 40 ° C. Alternatively, the separation of excess carbon monoxide can be achieved by so-called stripping of the catalyst or of the mixture containing the catalyst with a gas, advantageously with a gas which is inert under the reaction conditions. The term stripping the expert understands the introduction of a gas into the catalyst or the reaction mixture containing the catalyst such as in WRA Vauck, HA Müller, basic operations chemical engineering, German Verlag für Grundstoffchemie Leipzig, Stuttgart, 10th edition, 1984, page 800 , described. Examples of suitable inert gases include: hydrogen, helium, neon, argon, xenon, nitrogen and / or CO 2, preferably hydrogen, nitrogen, argon.

Preferably, the asymmetric hydrogenation is then carried out with hydrogen having a carbon monoxide content in the range of 50 to 3000 ppm, in particular in the range of 100 to 2000 ppm, especially in the range of 200 to 1000 ppm and especially in the range of 400 to 800 ppm.

If preformation of the rhodium catalyst is carried out, it is customary to dissolve the selected transition metal compound and the chiral ligand selected and, if desired, the substrate to be hydrogenated asymmetrically in a suitable, under the reaction conditions inert solvent or solvent medium such as ether, tetrahydrofuran, methyltetrahydrofuran, toluene, xylenes, chlorobenzene, octadecanol, biphenyl ether, Texanol, Marlotherm, Oxoöl 9N (hydroformylation products from isomeric octenes, BASF Aktiengesellschaft), citronellal and the like. The solution medium may also be the substrate to be reacted, the product or any high-boiling by-products obtained during the reaction. The resulting solution is, advantageously in a suitable pressure reactor or autoclave, at a pressure of usually about 5 to about 350 bar, preferably from about 20 to about 200 bar and more preferably from about 50 to about 100 bar pressed on a gas mixture, the hydrogen and carbon monoxide. Preference is given to preforming a gas mixture, about

From 30 to 99% by volume of hydrogen,

From 1 to 70% by volume of carbon monoxide and

Contains 0 to 5 vol .-% of other gases, the information must add up in vol .-% to 100 vol .-%.

Particular preference is given to preforming a gas mixture, about

40 to 80% by volume of hydrogen,

20 to 60% by volume of carbon monoxide and

A particularly preferred gas mixture for preforming is so-called synthesis gas, which usually consists of about 35 to 55% by volume of carbon monoxide in addition to hydrogen and traces of other gases.

The preforming of the catalyst is usually carried out at temperatures of about 25 ° C to about 100 ° C, preferably at about 40 ° C to about 80 ° C. If the preformation is carried out in the presence of the substrate to be asymmetrically hydrogenated, the temperature is advantageously chosen so that no isomerization of the double bond to be hydrogenated occurs to any extent. The preforming is usually completed after about 1 hour to about 24 hours, often after about 1 to about 12 hours. Following the optional preformation, the asymmetric hydrogenation of the selected substrate is carried out according to the invention. After previous preforming, the chosen substrate can usually be successfully orally charged with or without the addition of additional carbon monoxide. If no preforming is carried out, the asymmetric hydrogenation according to the invention can be carried out either in the presence of carbon monoxide fed to the reaction system or without the supply of carbon monoxide. Advantageously, preforming is carried out as described and additional carbon monoxide is added to the reaction mixture during the asymmetric hydrogenation.

If carbon monoxide is added to the reaction system, the feed can be carried out in various ways. For example, the carbon monoxide can be admixed with the hydrogen used for asymmetric hydrogenation or else be metered directly into the reaction solution in gaseous form. Another possibility is, for example, to add to the reaction mixture compounds that easily release carbon monoxide, such as formates or oxalyl compounds.

The carbon monoxide is preferably admixed with the hydrogen used for the asymmetric hydrogenation.

The asymmetric hydrogenation according to the invention is advantageously carried out at a pressure of about 2 to about 200 bar, in particular from about 10 to about 100 bar, especially at about 60 to about 100 bar and a temperature of usually about 0 ° C to about 100 ° C, preferably about 0 ° C to about 30 ° C, especially at about 10 ° C to about 30 ° C before.

The choice of the solvent to be used for carrying out the asymmetric hydrogenation according to the invention is of less importance. In any case, inventive advantages also occur in different solvents. Suitable solvents are, for example, those mentioned for carrying out the preforming according to the invention. With particular advantage, the asymmetric hydrogenation is carried out in the same solvent as the optionally previously performed preforming. Suitable reaction vessels for carrying out the asymmetric hydrogenation according to the invention are in principle all those which permit reactions under the conditions mentioned, in particular pressure and temperature, and are suitable for hydrogenation reactions, such as, for example, autoclaves, tubular reactors, bubble columns, etc. Carrying out the hydrogenation of the process according to the invention using high-boiling, generally viscous solvents, as described for example above for use in the pretreatment of the catalyst (such as the mentioned solvents octadecanol, biphenyl ether, Texanol, Marlotherm ^® , Oxoöl 9N) or if the hydrogenation is carried out without additional use of solvent, but with the high-boiling minor by-products (such as, for example, dimers or trimers, which are formed by reactions of the starting materials or products and subsequent secondary reactions) being used, it may be advantageous to to ensure good gas input and good mixing of gas phase and condensed phase. This is achieved, for example, by carrying out the hydrogenation step of the process according to the invention in a gas circulation reactor. Gas circulation reactors are known per se to those skilled in the art and are described, for example, in P. Trambouze, J.-P. Euzen, Chemical Reactors, Ed. Technip, 2004, pp. 280-283 and P. Zehner, R. Benfer, Chem. Eng. Be. 1996, 51, 1735-1744 and z. As described in EP 1 140 349. In principle, it is also possible to carry out the reaction in the product as a solvent, for example in citronellal, when the educt is neral or geranial. When using a gas circulating reactor as mentioned above, it has proved to be particularly advantageous to use the gas or gas mixture (carbon monoxide-containing hydrogen) in parallel to the educts introduced into the reactor and / or the circulating reaction mixture or the catalyst by means of a simple Nozzle or a two-fluid nozzle in the gas circulation reactor. In this case, the two-fluid nozzle is characterized in that to be introduced into the reactor

Liquid and gas pass through two separate nested tubes under pressure to the nozzle mouth where they are combined.

The process according to the invention can be carried out with good success with and without the addition of tertiary amines. Preferably, the inventive leads

Process in the absence, ie without the addition of additional tertiary amines or in the presence of only catalytic amounts of additional tertiary amines by. The amount of amine used may be between 0.5 and 500 molar equivalents based on the amount of metal used, but preferably 1 to 100 molar equivalents based on the amount of metal used. The choice of tertiary amine is not critical. In addition to short-chain alkylamines, such as triethylamine and long-chain alkyl amines, such as tridodecylamine, can be used. In a preferred embodiment, the hydrogenation process according to the invention is carried out. drive in the presence of a tertiary amine, preferably tridodecylamine, in an amount of about 2 to 30 molar equivalents, preferably about 5 to 20 molar equivalents and more preferably 5 to 15 molar equivalents based on the amount of transition metal used.

Advantageously, the reaction is stopped when the target compound in the desired yield and optical activity, i. is present in the reaction mixture with the desired enantiomeric excess (ee), as can be ascertained by the person skilled in the art by routine examinations, for example by means of chromatographic methods. Usually, the hydrogenation is completed after about 1 to about 150 hours, often after about 2 to about 24 hours.

The process of the invention makes it possible to provide optically active carbonyl compounds, in particular optically active aldehydes, in high yields and enantiomeric excesses. Usually, the desired asymmetrically hydrogenated compounds are obtained in an enantiomeric excess of at least 80% ee, often with an enantiomeric excess of from about 85 to about 99% ee. It should be noted that the maximum achievable enantiomeric excess may depend on the purity of the substrate used, in particular with regard to the isomeric purity of the double bond to be hydrogenated.

Accordingly, suitable starting substances in particular those having an isomer ratio of at least about 90:10, preferably at least about 95: 5 with respect to the E / Z double bond isomers.

By preforming and / or by additionally introduced into the reaction system carbon monoxide, the homogeneous catalysts used can be stabilized, whereby on the one hand the service life of the catalysts is significantly increased and on the other the reusability of the homogeneous catalysts is made possible.

For example, the resulting reaction product can be prepared by methods known to those skilled in the art, e.g. by distillation, remove from the reaction mixture and use the remaining catalyst, optionally after repeated preforming, in the context of further reactions.

Accordingly, the process according to the invention can be operated both batchwise or semicontinuously as well as continuously and is particularly suitable for reactions on an industrial scale. In a particularly preferred embodiment of the process according to the invention, neral or geranial, which contains up to about 5 mol%, preferably up to about 2 mol% of the particular double bond isomer, is converted to optically active citronellal. To form the catalyst, it is preferable to use a rhodium-soluble compound in the reaction mixture, in particular Rh (OAc) 3, [Rh (cod) Cl] 2,

Rh (CO) ₂ acac, [Rh (cod) OH] ₂ , [Rh (cod) OMe] ₂ , Rh ₄ (CO) i ₂ , Rh ₂ (OAc) ₄ ,

Bis (ethylene) rhodium (I) acetylacetonate or Rh6 (CO) i6 and as chiral ligands (R, R) - chiraphos or (S, S) -chiraphos ((2R, 3R) - (+) - 2,3- bis (diphenylphosphino) butane or (2S, 3S) - (-) - 2,3-bis (diphenylphosphino) butane) in a molar ratio of about 1: 1 to about 1: 4, wherein the reaction mixture during the hydrogenation of Neral or geranial additionally contains at least one compound of the general formula (I) which is in particular selected from one of the abovementioned compounds (1-1) to (1-12) and especially from

(5, S) -chiraphosmonooxide, cyclohexyldiphenylphosphine, cyclopentyldiphenylphosphine, 2-butyldiphenylphosphine or

Isopropyldiphenylphosphine, wherein the compound of formula (I) is used in particular in an amount of preferably 0.03 to 0.6 moles per mole of rhodium.

In a particularly preferred embodiment of the procedure according to the invention ren Substituting neral, up to about 5 mol%, preferably up to about contains 2 mol% geranial, in the presence of a soluble compound of rhodium in the reaction mixture, such as Rh (OAc) ₃ , [Rh (cod) Cl] ₂ , Rh (CO) ₂ acac, [Rh (cod) OH] ₂ , [Rh (cod) OMe] ₂ , Rh ₄ (CO) i ₂ , Rh ₂ (OAc) ₄ , Bis (ethylene) rhodium (l) acetylacetonate or Rh6 (CO) i6 and (R, R) -Chiraphos to D-citronellal, wherein the reaction mixture additionally contains during the hydrogenation at least one compound of general formula (I), in particular selected is among one of the aforementioned compounds (1-1) to (1-12) and especially under

(5, S) -chiraphosmonooxide, cyclohexyldiphenylphosphine, cyclopentyldiphenylphosphine, 2-butyldiphenylphosphine or isopropyldiphenylphosphine, wherein the compound of formula (I) is used in particular in an amount of 0.03 to 0.6 moles per mole of rhodium. In another, likewise particularly preferred embodiment of the process according to the invention, neral containing up to about 5 mol%, preferably up to about 2 mol%, of geranial is added in the presence of a rhodium-soluble compound of the rhodium, such as Rh (OAc). 3, [Rh (cod) Cl] ₂ , Rh (CO) ₂ acac, [Rh (cod) OH] ₂ , [Rh (cod) OMe] ₂ , Rh ₄ (CO) i ₂ , Rh ₂ (OAc) ₄ .

Bis (ethylene) rhodium (l) acetylacetonate or Rh6 (CO) i6 and (S, S) -Chiraphos to L-citronellal um, wherein the reaction mixture additionally contains during the hydrogenation at least one compound of general formula (I), in particular selected is among one of the aforementioned compounds (1-1) to (1-12) and especially under

(S, S) -chiraphosmonooxide, cyclohexyldiphenylphosphine, cyclopentyldiphenylphosphine, 2-butyldiphenylphosphine or isopropyldiphenylphosphine, wherein the compound of the formula (I) is used in particular in an amount of 0.03 to 0.6 mol per mol of rhodium. Preference is given to preforming the catalyst under the abovementioned conditions and then carrying out the asymmetric hydrogenation in the presence of hydrogen, which contains in particular 50 to 3000 ppm of carbon monoxide. Within the scope of the preferred embodiment, it is advantageous to dispense with the addition of solvents and to carry out the abovementioned reactions in the substrate or product to be reacted and, if appropriate, in high-boiling by-products as solvent medium. Particularly preferred is the continuous reaction with reuse or recycling of the invention stabilized homogeneous catalyst.

In principle, (R, R) -chiraphos can be replaced by (R, R) -noros ((2R, 3R) -2,3-bis (diphenylphosphino) bicyclo [2.2.1] hept-4-ene) or (S, S) -chiraphos by (S, S) - norphos ((2S, 3S) -2,3-bis (diphenylphosphino) bicyclo [2.2.1] hept-4-ene).

A further aspect of the present invention relates to a process for the preparation of optically active menthol using optically active citronellal prepared by the process according to the invention. The preparation of optically active menthol starting from optically active citronellal is known. A key step here is the cyclization of optically active citronellal to optically active isopulegol as described for example in EP-A 1 225 163. The process for preparing optically active menthol comprises the following steps: i) preparation of optically active citronellal by asymmetric hydrogenation of geranial of the formula (IIa-1) or of neral of the formula (IIb-1) by the process according to the invention,

ii) cyclization of the thus prepared optically active citronellal to optically active isopulegol in the presence of a Lewis acid and

iii) hydrogenation of the thus prepared optically active isopulegol to optically active menthol.

The optically active citronellal prepared according to the invention can be prepared, as shown schematically below for the preparation of L-menthol of the formula (XIII), in Presence of a suitable acid, in particular a Lewis acid to the L-isopulegol of the formula (XII) cyclize and then hydrogenated to L-menthol.

(VI) (XII) (XIII)

A further aspect of the present invention accordingly relates to the use of optically active citronellal prepared by the process according to the invention for the preparation of optically active menthol. In particular, the invention relates to the use of the D-citronellal prepared by the process according to the invention for the preparation of optically active L-menthol.

The following examples serve to illustrate the invention without affecting it in any way: EXAMPLES

Comparative Example 1 Asymmetric Hydrogenation of Neral in the Presence of Carbon Monoxide Rh (CO) ₂ acac (43 mg, 0.17 mmol) and (R, R) -chiraphos (105 mg, 0.24 mmol) were dissolved in Texanol (28 ml, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Sigma-Aldrich) and dissolved in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gasification stirrer, 1000 revolutions / min) at 80 bar synthesis gas (H2 / CO = 1: 1, v / v) and 70 ° C for 16 h. It is then cooled to 25 ° C and passed through the solution for two hours (8 l / h). After purging with nitrogen, neral (16.2 g, ratio of double bond isomers Neral / Geranial = 98.3: 0.4, substrate / catalyst molar ratio = 650) was added via a gate to the autoclave. The reaction pressure was adjusted to 80 bar by squeezing hydrogen gas containing 1000 ppm of carbon monoxide. Time / conversion was determined by gas chromatography. After 4 hours reaction time, a conversion of 39% and a yield of 39% of citronellal was achieved. After 20 h, the conversion of citral was> 99% and the yield of D-citronellal was also> 99%, the optical purity being determined to be 85% ee. Examples 2a-2o: Asymmetric hydrogenation of neral in the presence of carbon monoxide with the addition of a promoter (Table 1) at c (Rh) = 400 ppm

Rh (CO) ₂ acac (43 mg, 0.17 mmol), (R, R) -chiraphos (105 mg, 0.24 mmol) and an additive (see Table 1) were dissolved in Texanol (28 ml, 2 , 2,4-trimethyl-1,3-pentanediol monoisobutyrate, Sigma-Aldrich) and dissolved in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gasification stirrer, 1000 revolutions / min) at 80 bar synthesis gas (H ₂ / CO = 1: 1, v / v) and 70 ° C for 16 h. It is then cooled to 25 ° C and passed through the solution for two hours (8 l / h). After purging with nitrogen, 16.2 g of neral (ratio of double bond isomers Neral / Geranial = 98.3: 0.4, substrate / catalyst ratio = 650) were added to the autoclave via a sluice. The reaction pressure was adjusted to 80 bar by squeezing hydrogen gas containing 1000 ppm of carbon monoxide. Time / conversion was determined by gas chromatography. Sales / enantioselectivities / additives are given in Table 1.

Example 2p-q: Asymmetric hydrogenation of neral in the presence of carbon monoxide with addition of a promoter (Table 1) at c (Rh) = 700 ppm Rh (CO) ₂ acac (75 mg, 0.29 mmol), (R, R) Chiraphos (186 mg, 0.44 mmol) and an additive (see Table 1) were dissolved in Texanol (28 ml, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Sigma-Aldrich) and dissolved in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled Begasungsrührer, 1000 revolutions / min) at 80 bar synthesis gas (H ₂ / CO = 1: 1, Vol.A / ol.) And 70 ° C for 16 h. It is then cooled to 25 ° C and passed through the solution for two hours (8 l / h). After purging with nitrogen, 16.2 g of neral (ratio of double bond isomers Neral / Geranial = 98.3: 0.4, substrate / catalyst ratio = 365) were added to the autoclave via a sluice. The reaction pressure was adjusted to 80 bar by squeezing hydrogen gas containing 1000 ppm of carbon monoxide. Time / conversion was determined by gas chromatography. Sales / enantioselectivities / additives are given in Table 1.

Comparative Examples 2r-s: Asymmetric hydrogenation of neral in the presence of carbon monoxide upon addition of the promoter without bidentate ligands (Table 1) at c (Rh) = 400 ppm

Rh (CO) ₂ acac (43 mg, 0.17 mmol) and the phosphine ligand (0.17 mmol, see Table 1) were dissolved in Texanol (28 mL, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Sigma-Aldrich) and dissolved in a 100 ml steel autoclave (V2A steel, manufacturer Premex, magnetically coupled gassing stirrer, 1000 revolutions / min) at 80 bar synthesis gas (H ₂ / CO = 1: 1, v / v). and 70 ° C for 16 h. It is then heated to 25 ° C cooled and passed through the solution for two hours (8 l / h). After purging with nitrogen, 16.2 g of neral (ratio of the double bond isomers neutral / geranial = 98.3: 0.4, substrate / catalyst ratio = 650) were added to the autoclave via a sluice. The reaction pressure was adjusted to 80 bar by pressing hydrogen gas containing 1000 ppm of carbon monoxide. Time / conversion was determined by gas chromatography. Sales and enantioselectivities are given in Table 1.

Comparative Example 2t

The reaction was carried out according to the procedure described for Example 2b, with the solvent Texanol being replaced by the same amount of D-citronellal (88% ee) and no (R, R) -chiraphosmonoxide being added as an additive to the reaction mixture. Sales and enantioselectivities are given in Table 1.

Example 2u:

The reaction was carried out according to the procedure described for Example 2b, with the solvent Texanol being replaced by the same amount of D-citronellal (88% ee). Sales and enantioselectivities are given in Table 1.

Comparative Example 2v

The reaction was carried out according to the procedure described for Example 2b, wherein (R, R) -Chiraphos was replaced by the same amount of (R, R) -Norphos and no (R, R) -chiraphosmonoxide was added as an additive to the reaction mixture has been. Sales and enantioselectivities are given in Table 1.

Example 2w:

The reaction was carried out according to the procedure described for example 2b, wherein (R, R) -chiraphos was replaced by the same amount of (R, R) -norphos. Sales and enantioselectivities are given in Table 1. Example 2x:

The reaction was carried out according to the procedure described for Example 2b, using pure hydrogen instead of the carbon monoxide-containing hydrogen. Sales and enantioselectivities are given in Table 1.

Comparative Example 2y The reaction was carried out according to the procedure described for Example 2a, wherein the reaction mixture 1, 05 mmol tridodecylamine was added as an additive. Sales and enantioselectivities are given in Table 1. Example 2z:

The reaction was carried out according to the procedure described for Example 2y, with chiraphosmonoxide being added as an additive to the reaction mixture in addition to the tridodecylamine (R, R). Sales and enantioselectivities are given in Table 1.

Example 3: Preparation of (R, R) -chiraphosmonooxide (CPMO) by oxidation of (R, R) -chiraphos with hydrogen peroxide (R, R) -chiraphos (230 g, 0.54 mol) in a 5 L double-walled stirred vessel dissolved in toluene (3500 ml) with stirring at 25 ° C. and hydrogen peroxide (15% in water, 9 g, 0.26 mol) was continuously added over 8 hours via a spray pump. The temperature is maintained at 25 ° C (the temperature increase caused by exothermic is minimal). The reaction is stirred overnight for a further 10 hours at 25 ° C. The reaction effluent is concentrated on a rotary evaporator at 150 mbar and 75 ° C to 900 ml (clear yellowish solution). 100 ml of the concentrated solution are completely concentrated at 75 ° C / 5 mbar and purified in the glove box on a 10 ^* 10 cm silica gel column. Separation of unreacted chirosphosphate is first eluted with toluene (1500 mL), then with methanol (600 mL), control of fractions by GC (column: 30m / 0.32mm HP-5, injector: 280 ° C , Detector: FID, 320 ° C, program: 100 ° C - »20 ° C / min -» 300 ° C. There are obtained 3.1 g of a mixture of CPMO: CPDO = 76:24 (based on ³¹ P-NMR). ³¹ P-NMR (C ₆ D ₆ , 500 MHz): 33.5 ppm (CPDO), 33.0 ppm (d, 30 Hz), -8.1 ppm (d, 30 Hz) Table 1: Overview of the Results of Examples 1 and 2a s

Example Compound (I) ^a > mol% bezoc (Rh, total) 4 h 20 h% ee

[mmol] gen to Chi- [ppm] [%] ^e > [%] "

raphos

1 ^* ) - - 400 39> 99 85

2a CPMO ^b > (0.066) 26% 400 93> 99 87

2b CPMO ^b > (0.075) 30% 400 97> 99 87

2c ^* ) TPP 10% 400 45 98 85

(0.028)

2d ^* ) TPP 30% 400 44> 99 87

(0,081) Example Compound (l) ^a > mol% bezoc (Rh, total) 4 h 20 h% ee [mmol] gen to Chi- [ppm] [%] ^e > [%] "

raphos

2e CyDPP 10% 400 68> 99 85

(0.026)

2f CyDPP 30% 400 98> 99 87

(0.077)

2g iPrDPP 10% 400 57 97 84

(0.028)

2h iPrDPP 30% 400 95> 99 87

(0.076)

2i ^*) HexDPP 10% 400 34 99 83

(0.025)

2j ^*) HexDPP 30% 400 33> 99 87

(0.076)

2k CPMO ^b > 10% 400 55> 99 87

(0.024)

21 CPMO ^b > (0.034) 15% 400 84> 99 87

2m ^*) DPPE-0 10% 400 28 98 83

2n ^*) DPPE-0 30% 400 26 98 85

2o ^*) CPDO 30% 400 23> 99 84

2p ^*) - - 700 75> 99 87

2q CPMO ^b > (0.130) 30% 700>99> 99 87

2r ^*) only CPMO ^b > CMPO: Rh = 400 1 1 nb ^d >

1: 1

2s ^*) only iPrDPP iPrDPP: Rh = 400 4 6 nb ^d >

1: 1

2t * ⁾ 9) - - 400 68> 99 89

2u 9) CPMO> (0.075) 30% 400 79> 99 89

2v ^{*) h} > - - 400 14 70 83

2w ^h >CPMO> (0.075) 30% 400 41 95 84

2x o CPMO> (0.075) 30% 400 88 98 87

2y ^*) tridodecylamine 400% 400 54 99 86

(1, 05)

2z tridodecylamine 400% 400 97 99 86

(1, 05)

CPMO> (0.075) 30%

^* ) The examples marked with an asterisk are comparative examples. a) see Table 2;

b) CPMO was added as a mixture of 75% CPMO with 23% CPDO (preparation according to Example 3); the amount added refers to the added amount of pure CPMO in this mixture;

d) not determined, too low turnover;

e) sales after 4h;

f) turnover after 20 h;

g) The solvent Texanol was replaced by D-citronellal (88% ee);

h) (R, R) -Chiraphos has been replaced by (R, R) -Norphos;

i) Hydrogen supplied contains no CO.

Table 2: Ligand structures

Claims

claims:

Process for the preparation of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α, β-unsaturated carbonyl compound with hydrogen in the presence of at least one reaction mixture-soluble, optically active transition metal catalyst comprising rhodium as the catalytically active transition metal and a chiral bidentate bisphosphine ligand, wherein during the hydrogenation of the prochiral α, β-unsaturated carbonyl compound the reaction mixture additionally contains at least one compound of the general formula (I):

R

I

2.

(I)

in which R ¹ , R ^{2 are} identical or different and are C 6 - to C 10 -aryl unsubstituted or bearing one or more substituents selected from C 1 to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C6 to Cio-aryl, Cr to C6-alkoxy and amino; is a group CHR ³ R ⁴ or aryl which is unsubstituted or bears one or more substituents selected from C 1 to C 6 alkyl, C ^{3 to} C 6 cycloalkyl, C 6 to C 10 aryl, C 1 to C 6 alkoxy and amino wherein for d- to C ₄ alkyl, d- to C ₄ -alkoxy-d- alkyl to C _4, C ₃ - to C ₆ - cycloalkyl or C6 is to Cio-aryl, wherein one or two non-adjacent CH 2 groups in C 3 to C 6 cycloalkyl may also be replaced by an oxygen atom; C 1 to C ₄ -alkyl which is unsubstituted or carries a group P (= O) R ^4a R ^4b , C 1 to C ₄ -alkoxy, C 1 to C ₄ -alkoxy-C 1 to C ₄ -alkyl, C ₃ - to C6-cycloalkyl or C6- to Cio-aryl, wherein one or two non-adjacent CH2 groups in C3- to C6-cycloalkyl may also be replaced by an oxygen atom and wherein C3- to C6-cycloalkyl and C6- to Cio -Aryl are unsubstituted or carry one or more substituents selected from C 1 to C ₄ alkyl, C 1 to C ₄ alkoxy and amino; or R ³ , R ⁴ : together with the C-atom to which they are attached, is C ₄ - to Ce-cycloalkyl, in which one or two non-adjacent Ch groups in C ₃ to C ₆ cycloalkyl is also replaced by an oxygen atom and wherein C3 to C6 cycloalkyl is unsubstituted or carries one or more Subsitutenten selected from Cr to C ₄ alkyl, Cr to C ₄ alkoxy and

AP (= 0) R ^4a R ^4b , wherein A is a chemical bond or Cr to C ₄ alkylene; and

R ^4a , R ^4b : are the same or different and are phenyl which is unsubstituted or carries one or more substituents selected from C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, C 6 to C 10 aryl, Cr to C6-alkoxy and amino.

2. The method of claim 1, wherein Z in formula (I) is a group CHR ³ R ⁴ .

A method according to claim 2, wherein the variables R ¹ , R ² , Z in formula (I) have the following meanings: the same or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from Methyl and methoxy; is a group CHR ³ R ⁴ wherein R ^{3 is} Cr to C ₄ alkyl;

R ^{4 is} C ₄ to C ₄ alkyl which is unsubstituted or a group

P (= 0) carries R ^4a R ^4b ; or

R ³ , R ⁴ : together with the carbon atom to which they are attached, is C ³ -C ⁶ -cycloalkyl in which one or two Ch groups may be replaced by one or two oxygen atoms and where C ³ to C ⁶ Cycloalkyl is unsubstituted or carries a group AP (= O) R ^4a R ^4b and / or has 1, 2, 3 or 4 methyl groups as substituents; where A is a chemical bond, CH 2 or CH (CH 3);

and are the same or different and are C6 to Cio-aryl, which is unsubstituted or carries 1, 2 or 3 substituents selected from methyl and methoxy.

The method of claim 2, wherein are unsubstituted phenyl;

R ^{3 is} methyl;

A process according to any one of the preceding claims wherein the compound of formula (I) is used in an amount of from 0.001 mole to 1 mole per mole of rhodium.

A process according to any one of the preceding claims wherein the prochiral α, β-unsaturated carbonyl compound is a prochiral, α, β-unsaturated ketone or a prochiral, α, β-unsaturated aldehyde.

7. The method according to any one of the preceding claims, wherein the prochiral α, β-unsaturated carbonyl compound is selected from compounds of general formula (II)

wherein

R ⁵ , R ⁶ are different from each other and each represents an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more non-conjugated ethylenic double bonds and which is unsubstituted or one or more identical or different Carries substituents selected from OR ⁸ , NR ^9a R ^9b , halogen, C6 to Cio-aryl and C3 to Cg-hetaryl;

R ^{7 is} hydrogen or an unbranched, branched or cyclic hydrocarbon radical having from 1 to 25 carbon atoms which is saturated or has one or more non-conjugated ethylenic double bonds and which is unsubstituted or one or more identical or different substituents which are selected from OR ⁸ , NR ^9a R ^9b , halogen, Ce to C10 aryl and C3 to Cg hetaryl; or

R ^{7 may} together with one of the radicals R ⁵ or R ⁶ also denote a 3 to 25-membered alkylene group wherein 1, 2, 3 or 4 non-adjacent Ch groups may be replaced by O or NR ^9c , wherein the alkylene group is saturated or has one or more non-conjugated ethylenic double bonds, and wherein the

Alkylene group is unsubstituted or carries one or more identical or different substituents selected from OR ⁸ , NR ^9a R ^9b , halogen, Cr to C ₄ alkyl, C ₆ - to Cio-aryl and C ₃ - to Cg-hetaryl, wherein two substituents may also together represent a 2- to 10-membered alkylene group, wherein the 2- to

10-membered alkylene group is saturated or has one or more non-conjugated ethylenic double bonds, and wherein the 2- to 10-membered alkylene group is unsubstituted or carries one or more identical or different substituents selected from OR ⁸ , NR ^9a R ^9b , Halogen, C ₆ - to Cio-aryl and C 3 - to Cg-hetaryl; wherein R ⁸ is hydrogen, d- to C ₆ alkyl, C ₆ - to Cio-aryl, C ₇ - to C ₂ -aralkyl or C7 to Ci2-is alkylaryl;

R ^9a , R ^{9b are} each independently hydrogen, C 1 to C 6 alkyl, C 6 to C 10 aryl, C 7 to C 12 aralkyl or C 7 to C 12 alkylaryl or

R ^9a and R ^9b together may also denote an alkylene chain of 2 to 5 carbon atoms which may be interrupted by N or O; is Ci to ₂ -aralkyl or C7-Ci2-alkyl-aryl - and are hydrogen, d- to C ₆ alkyl, C ₆ - to Cio-aryl, C. ₇

8. The method according to any one of the preceding claims, wherein the prochiral α, β-unsaturated carbonyl compound is selected from compounds of the general formula (IIa) and (IIb)

R ⁵ , R ⁶ each represents a straight or branched hydrocarbon radical having 2 to 25 carbon atoms, which is saturated or has 1, 2, 3, 4 or 5 nonconjugated ethylenic double bonds;

Process according to Claim 8 for the preparation of optically active citronellal of the formula (IV)

in which ^{* designates} the center of asymmetry; by asymmetric hydrogenation of geranial of the formula (IIa-1) or of neral of the formula (IIb-1)

10. The method of claim 9 for the preparation of D-citronellal by asymmetric hydrogenation of Neral.

1 1. A process according to any one of the preceding claims wherein the chiral bidentate bisphosphine ligand is a compound of general formulas (IX), (X) or (XI):

(IX)

(X) wherein

R ¹¹ , R ¹² : each independently represent an unbranched, branched or cyclic hydrocarbon radical having 1 to 20 carbon atoms, which is saturated or may have one or more, usually 1 to about 4, non-conjugated, ethylenic double bonds, and which is unsubstituted or bears one or more, usually 1 to 4, identical or different substituents selected from OR ¹⁹ , NR ²⁰ R ²¹ , halogen, C ₆ -C 10 -aryl and Cs-Cg-hetaryl, or

R ¹⁵ , R ¹⁶ , R ¹⁷ , R ^{18 are the} same or different and are C ⁶ to C 10 aryl which is unsubstituted or carries one or more substituents selected from C 1 to C 6 alkyl, C 3 to C6 cycloalkyl, C6 to Cio aryl, C6 to C6 alkoxy and amino; R ¹⁹ , R ²⁰ , R ²¹ : in each case independently of one another hydrogen, C 1 -C 4 -alkyl,

C6-Cio-aryl, C7-Ci2-aralkyl or C7-Ci2-alkylaryl, where together also an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O may mean.

The method of claim 1 1, wherein the chiral bidentate bisphosphine ligand is a compound of the general formula (IX).

The method of claim 12, wherein the chiral bidentate bisphosphine is either the compound of formula (IXa) or of formula (IXb):

Ph ₂ P PPh ₂ Ph ₂ P PPh ₂

(IXa) (IXb) wherein Ph is phenyl.

The method of claim 12, wherein the chiral bidentate bisphosphine ligand is either the compound of formula (IXc) or or of formula (IXd):

(IXd) (IXd) wherein Ph is phenyl.

15. The method according to any one of the preceding claims, having at least one or all of the following features a - g: a) carrying out the asymmetric hydrogenation at a hydrogen pressure of 5 to 200 bar, in particular at a hydrogen pressure of 10 to 100 bar ;

b) Continuous implementation of the process;

c) in situ generation of the catalyst before or during the hydrogenation by

Reaction of an achiral rhodium compound and with a chiral bidentate bisphosphine ligand; d) pretreatment of the catalyst before the hydrogenation with a carbon monoxide and hydrogen-containing gas mixture;

e) carrying out the asymmetric hydrogenation in the presence of carbon monoxide additionally supplied to the reaction mixture;

f) carrying out the asymmetric hydrogenation with hydrogen having a carbon monoxide content in the range of 50 to 3000 ppm, in particular in the range of 100 to 2000 ppm, especially in the range of 200 to 1000 ppm and more particularly in the range of 400 to 800 ppm;

g) carrying out the asymmetric hydrogenation in a gas circulation reactor; h) carrying out the asymmetric hydrogenation in a gas circulation reactor, wherein the reacted α, β-unsaturated carbonyl compound and the hydrogen is introduced by means of a two-fluid nozzle in the gas circulation reactor.

Process for the preparation of optically active menthol comprising the steps i) Preparation of optically active citronellal by asymmetric hydrogenation according to claim 9 of geranial of the formula (IIa-1) or of neral of the formula (IIb-1),